scholarly journals Spirulina supplementation in a mouse model of diet-induced liver fibrosis reduced the pro-inflammatory response of splenocytes

2019 ◽  
Vol 121 (7) ◽  
pp. 748-755 ◽  
Author(s):  
Tho X. Pham ◽  
Yoojin Lee ◽  
Minkyung Bae ◽  
Siqi Hu ◽  
Hyunju Kang ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Mouse Model ◽  
High Cholesterol Diet ◽  
Appreciable Effect ◽  
Healthy Foods ◽  
Inflammatory Gene Expression ◽  
Inflammatory Conditions ◽  
Alanine Aminotransferase Level ◽  
High Sucrose

AbstractTreatment of liver fibrosis is very limited as there is currently no effective anti-fibrotic therapy. Spirulina platensis (SP) is a blue-green alga that is widely supplemented in healthy foods. The objective of this study was to determine whether SP supplementation can prevent obesity-induced liver fibrosis in vivo. Male C57BL/6J mice were randomly assigned to a low-fat or a high-fat (HF)/high-sucrose/high-cholesterol diet or an HF diet supplemented with 2·5 % SP (w/w) (HF/SP) for 16 or 20 weeks. There were no significant differences in body weight, activity, energy expenditure, serum lipids or glucose tolerance between mice on HF and HF/SP diets. However, plasma alanine aminotransferase level was significantly reduced by SP at 16 weeks. Expression of fibrotic markers and trichrome stains showed no differences between HF and HF/SP. Splenocytes isolated from HF/SP fed mice had lower inflammatory gene expression and cytokine secretion compared with splenocytes from HF-fed mice. SP supplementation did not attenuate HF-induced liver fibrosis. However, the expression and secretion of inflammatory genes in splenocytes were significantly reduced by SP supplementation, demonstrating the anti-inflammatory effects of SP in vivo. Although SP did not show appreciable effect on the prevention of liver fibrosis in this mouse model, it may be beneficial for other inflammatory conditions.

scholarly journals Effects of Thymus vulgaris L., Cinnamomum verum J.Presl and Cymbopogon nardus (L.) Rendle Essential Oils in the Endotoxin-induced Acute Airway Inflammation Mouse Model

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3553
Author(s):  
Eszter Csikós ◽  
Kata Csekő ◽  
Amir Reza Ashraf ◽  
Ágnes Kemény ◽  
László Kereskai ◽  
...  
Keyword(s):  
Mouse Model ◽  
Essential Oils ◽  
Airway Inflammation ◽  
Airway Hyperresponsiveness ◽  
Whole Body ◽  
Gas Chromatography Mass Spectrometry ◽  
Thymus Vulgaris ◽  
Inflammatory Conditions ◽  
Inflammatory Parameters

Thyme (TO), cinnamon (CO), and Ceylon type lemongrass (LO) essential oils (EOs) are commonly used for inhalation. However, their effects and mechanisms on inflammatory processes are not well-documented, and the number of in vivo data that would be important to determine their potential benefits or risks is low. Therefore, we analyzed the chemical composition and investigated the activity of TO, CO, and LO on airway functions and inflammatory parameters in an acute pneumonitis mouse model. The components of commercially available EOs were measured by gas chromatography–mass spectrometry. Airway inflammation was induced by intratracheal endotoxin administration in mice. EOs were inhaled during the experiments. Airway function and hyperresponsiveness were determined by unrestrained whole-body plethysmography on conscious animals. Myeloperoxidase (MPO) activity was measured by spectrophotometry from lung tissue homogenates, from which semiquantitative histopathological scores were assessed. The main components of TO, CO, and LO were thymol, cinnamaldehyde, and citronellal, respectively. We provide here the first evidence that TO and CO reduce inflammatory airway hyperresponsiveness and certain cellular inflammatory parameters, so they can potentially be considered as adjuvant treatments in respiratory inflammatory conditions. In contrast, Ceylon type LO inhalation might have an irritant effect (e.g., increased airway hyperresponsiveness and MPO activity) on the inflamed airways, and therefore should be avoided.

S1595 Rapid Predictive Mouse Model of Parenchymal Liver Fibrosis for Antifibrotic Drug Screening In Vivo

2009 ◽  
Vol 136 (5) ◽  
pp. A-821
Author(s):  
Yury Popov ◽  
Deanna Sverdlov ◽  
Anisha Sharma ◽  
Rohan Akhouri ◽  
Thomas Konturek ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Mouse Model ◽  
Drug Screening ◽  
Parenchymal Liver

Accumulating bile salts promote liver fibrosis in cholestasis: in vivo evidence in a mouse model

2019 ◽  
Author(s):  
S Hohenester ◽  
R Wimmer ◽  
AE Kremer ◽  
G Denk ◽  
R Florian ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Mouse Model ◽  
Bile Salts

scholarly journals Nicotinamide Riboside, an NAD + Precursor, Reduces Hepatic Stellate Cell Activation and Attenuates Liver Fibrosis in a Diet-induced Mouse Model of Liver Fibrosis (OR24-06-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Tho Pham ◽  
Minkyung Bae ◽  
Mi-Bo Kim ◽  
Yoojin Lee ◽  
Siqi Hu ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Energy Expenditure ◽  
Mouse Model ◽  
Cell Activation ◽  
Stellate Cell ◽  
Body Weight Gain ◽  
Nicotinamide Riboside ◽  
Primary Mouse

Abstract Objectives There is limited pharmacological treatment for liver fibrosis, which can result from chronic liver injury. In this study, we investigated the effect of nicotinamide riboside (NR), a nicotinamide adenine dinucleotide (NAD) precursor, on the development of liver fibrosis in a diet-induced mouse model of liver fibrosis in vivo and in hepatic stellate cells (HSCs) in vitro. Methods Male C57BL/6 J mice were randomly assigned to three groups: a low-fat control (LF; 6% fat by wt), a high-fat/high-sucrose/high-cholesterol control (HF; 35%/34%/2.0% by wt, n = 13) or a HF diet supplemented with NR at 400 mg/kg/day (HF-NR, n = 14) for 20 weeks. Features of liver fibrosis were assessed by molecular, histological, and biochemical analyses to determine the effect of NR. Metabolic rates, energy expenditure and physical activity were measured using indirect calorimetry. Primary mouse and human HSCs, the primary extracellular matrix-producing cell-type in the liver, were used to determine the anti-fibrogenic effects of NR in vitro. Results HF-NR group had reduced body weight gain, which was attributable to increased energy expenditure. NR supplementation did not affect serum alanine aminotransferase levels and markers of steatosis and inflammation in the liver. However, liver trichrome and picrosirius red staining and total collagen quantification showed significant reductions of collagen by NR. Consistently, hepatic collagen 1a1 mRNA and protein were significantly reduced in the HF-NR group. Liver NAD levels were significantly reduced by HF, but was increased by NR supplementation. RNA-Seq analysis of NAD metabolism genes in quiescent and activated HSCs indicated that NAD levels might be reduced in activated HSCs due to repression of NAD salvage pathway, which regenerates NAD from nicotinamide. Indeed, treatment of primary human and mouse HSCs with NR significantly reduced their activation in vitro. Conclusions NR supplementation prevented the development of liver fibrosis in a diet-induced mouse model of liver fibrosis independent of hepatic steatosis and inflammation. The data suggest that NR may directly reduce HSC activation to exert its anti-fibrotic effect. NR may be developed as a potential preventative for human liver fibrosis. Funding Sources The NIH, USDA Multistate Hatch, and USDA Hatch.

scholarly journals D-mannose suppresses macrophage IL-1β production

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Simone Torretta ◽  
Alessandra Scagliola ◽  
Luisa Ricci ◽  
Francesco Mainini ◽  
Sabrina Di Marco ◽  
...  
Keyword(s):  
Mouse Model ◽  
Macrophage Activation ◽  
T Cell Differentiation ◽  
Activated Macrophages ◽  
Phosphomannose Isomerase ◽  
Inflammatory Conditions ◽  
Consequent Reduction ◽  
Inflammatory Macrophages ◽  
Mannose Metabolism

AbstractD-mannose is a monosaccharide approximately a hundred times less abundant than glucose in human blood. Previous studies demonstrated that supraphysiological levels of D-mannose inhibit tumour growth and stimulate regulatory T cell differentiation. It is not known whether D-mannose metabolism affects the function of non-proliferative cells, such as inflammatory macrophages. Here, we show that D-mannose suppresses LPS-induced macrophage activation by impairing IL-1β production. In vivo, mannose administration improves survival in a mouse model of LPS-induced endotoxemia as well as decreases progression in a mouse model of DSS-induced colitis. Phosphomannose isomerase controls response of LPS-activated macrophages to D-mannose, which impairs glucose metabolism by raising intracellular mannose-6-phosphate levels. Such alterations result in the suppression of succinate-mediated HIF-1α activation, imposing a consequent reduction of LPS-induced Il1b expression. Disclosing an unrecognized metabolic hijack of macrophage activation, our study points towards safe D-mannose utilization as an effective intervention against inflammatory conditions.

scholarly journals In Vivo Colonization with Candidate Oral Probiotics Attenuates Colonization and Virulence of Streptococcus mutans

2020 ◽  
Author(s):  
David. J. Culp ◽  
William Hull ◽  
Matthew J. Bremgartner ◽  
Todd A. Atherly ◽  
Kacey N. Christian ◽  
...  
Keyword(s):  
Dental Caries ◽  
Mouse Model ◽  
Streptococcus Mutans ◽  
Arginine Deiminase ◽  
Oral Streptococci ◽  
Study Results ◽  
Autochthonous Bacteria ◽  
High Sucrose

A collection of 113 Streptococcus strains from supragingival dental plaque of caries-free individuals were recently tested in vitro for direct antagonism of the dental caries pathogen Streptococcus mutans, and for their capacity for arginine catabolism via the arginine deiminase system (ADS). To advance their evaluation as potential probiotics, twelve strains of commensal oral streptococci with various antagonistic and ADS potentials were assessed in a mouse model for oral (i.e., oral mucosal pellicles and saliva) and dental colonization under four diets (healthy or high-sucrose, with or without prebiotic arginine). Colonization by autochthonous bacteria was also monitored. One strain failed to colonize, whereas oral colonization by the other eleven strains varied by 3 log units. Dental colonization was high for five strains regardless of diet, six strains increased colonization with at least one high-sucrose diet, and added dietary arginine decreased dental colonization of two strains. Streptococcus sp. A12 (high in vitro ADS activity and antagonism) and two engineered mutants lacking the ADS (ΔarcADS) or pyruvate oxidase-mediated H2O2 production (ΔspxB) were tested for competition against S. mutans UA159. A12 wild type and ΔarcADS colonized only transiently, whereas ΔspxB persisted, but without altering oral or dental colonization by S. mutans. In testing four additional candidates, S. sanguinis BCC23 markedly attenuated S. mutans’ oral and dental colonization, enhanced colonization of autochthonous bacteria, and decreased severity of smooth surface caries under highly cariogenic conditions. Results demonstrate the utility of the mouse model to evaluate potential probiotics, revealing little correlation between in vitro antagonism and competitiveness against S. mutans in vivo. IMPORTANCE Our results demonstrate in vivo testing of potential oral probiotics can be accomplished and can yield information to facilitate the ultimate design and optimization of novel anti-caries probiotics. We show human oral commensals associated with dental health are an important source of potential probiotics that may be used to colonize patients under dietary conditions of highly varying cariogenicity. Assessment of competitiveness against dental caries pathogen Streptococcus mutans and impact on caries identified strains or genetic elements for further study. Results also uncovered strains that enhanced oral and dental colonization by autochthonous bacteria when challenged with S. mutans, suggesting cooperative interactions for future elucidation. Distinguishing a rare strain that effectively compete with S. mutans under conditions that promote caries further validates our systematic approach to more critically evaluate probiotics for use in humans.

TGF-β1 in liver fibrosis: an inducible transgenic mouse model to study liver fibrogenesis

1999 ◽  
Vol 276 (4) ◽  
pp. G1059-G1068 ◽  
Author(s):  
Stephan Kanzler ◽  
Ansgar W. Lohse ◽  
Andrea Keil ◽  
Jürgen Henninger ◽  
Hans P. Dienes ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Plasma Levels ◽  
Transgenic Animals ◽  
Transgenic Mouse Model ◽  
Transgenic Lines ◽  
Liver Fibrogenesis ◽  
Tgf Β1

Transforming growth factor-β1 (TGF-β1) is a powerful stimulus for collagen formation in vitro. To determine the in vivo effects of TGF-β1 on liver fibrogenesis, we generated transgenic mice overexpressing a fusion gene [C-reactive protein (CRP)/TGF-β1] consisting of the cDNA coding for an activated form of TGF-β1 under the control of the regulatory elements of the inducible human CRP gene promoter. Two transgenic lines were generated with liver-specific overexpression of mature TGF-β1. After induction of the acute phase response (15 h) with lipopolysaccharide (100 μg ip), plasma TGF-β1 levels reached >600 ng/ml in transgenic animals, which is >100 times above normal plasma levels. Basal plasma levels of uninduced transgenic animals were about two to five times above normal. As a consequence of hepatic TGF-β1 expression, we could demonstrate marked transient upregulation of procollagen I and procollagen III mRNA in the liver 15 h after the peak of TGF-β1 expression. Liver histology after repeated induction of transgene expression showed an activation of hepatic stellate cells in both transgenic lines. The fibrotic process was characterized by perisinusoidal deposition of collagen in a linear pattern. This transgenic mouse model gives in vivo evidence for the important role of TGF-β1 in stellate cell activation and liver fibrogenesis. Due to the ability to control the level of TGF-β1 expression, this model allows the study of the regulation and kinetics of collagen synthesis and fibrolysis as well as the degree of reversibility of liver fibrosis. The CRP/TGF-β1 transgenic mouse model may finally serve as a model for the testing of antifibrogenic agents.

scholarly journals Human Muse Cells, Nontumorigenic Phiripotent-Like Stem Cells, Have Liver Regeneration Capacity through Specific Homing and Cell Replacement in a Mouse Model of Liver Fibrosis

2017 ◽  
Vol 26 (5) ◽  
pp. 821-840 ◽  
Author(s):  
Masahiro Iseki ◽  
Yoshihiro Kushida ◽  
Shohei Wakao ◽  
Takahiro Akimoto ◽  
Masamichi Mizuma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Liver Fibrosis ◽  
Mouse Model ◽  
Liver Regeneration ◽  
Intravenous Injection ◽  
Functional Markers ◽  
Muse Cells

Muse cells, a novel type of nontumorigenic pluripotent-like stem cells, reside in the bone marrow, skin, and adipose tissue and are collectable as cells positive for pluripotent surface marker SSEA-3. They are able to differentiate into cells representative of all three germ layers. The capacity of intravenously injected human bone marrow-derived Muse cells to repair an immunodeficient mouse model of liver fibrosis was evaluated in this study. The cells exhibited the ability to spontaneously differentiate into hepatoblast/hepatocyte lineage cells in vitro. They demonstrated a high migration capacity toward the serum and liver section of carbon tetrachloride-treated mice in vitro. In vivo, they specifically accumulated in the liver, but not in other organs except, to a lesser extent, in the lungs at 2 weeks after intravenous injection in the liver fibrosis model. After homing, Muse cells spontaneously differentiated in vivo into HepPar-1 (71.1±15.2%), human albumin (54.3±8.2%), and anti-trypsin (47.9±4.6%)-positive cells without fusing with host hepatocytes, and expressed mature functional markers such as human CYP1A2 and human Glc-6-Pase at 8 weeks after injection. Recovery in serum, total bilirubin, and albumin and significant attenuation of fibrosis were recognized with statistical differences between the Muse cell-transplanted group and the control groups, which received the vehicle or the same number of a non-Muse cell population of MSCs (MSCs in which Muse cells were eliminated). Thus, unlike ESCs and iPSCs, Muse cells are unique in their efficient migration and integration into the damaged liver after intravenous injection, nontumorigenicity, and spontaneous differentiation into hepatocytes, rendering induction into hepatocytes prior to transplantation unnecessary. They may repair liver fibrosis by two simple steps: expansion after collection from the bone marrow and intravenous injection. A therapeutic strategy such as this is feasible and may provide significant advancements toward liver regeneration in patients with liver disease.

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